The primary treatment involves mechanical ventilation together with treatments directed at the underlying cause.[1] Ventilation strategies include using low volumes and low pressures.[1] If oxygenation remains insufficient lung recruitment maneuvers and paralysis may be tried.[1] If this is insufficient ECMO may be an option.[1] The syndrome is associated with a death rate between 35 and 50%.[1]

ARDS affects about 3 million people a year.[1] The condition was first described in 1967.[1] Although the terminology of "adult respiratory distress syndrome" has at times been used to differentiate ARDS from "infant respiratory distress syndrome" in newborns, the international consensus is that "acute respiratory distress syndrome" is the best term because ARDS can affect people of all ages.[3]

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ARDS is the severe form of acute lung injury (ALI) and of transfusion-related acute lung injury (TRALI). The Berlin definition included ALI as a mild form of ARDS.[4] However, the criteria for the diagnosis of ARDS in the Berlin definition excludes many children and a new definition for children was called pediatric acute respiratory distress syndrome (PARDS). This is known as the PALLIC definition.[5][6]

Diffuse compromise of the pulmonary system resulting in ARDS generally occurs in the setting of critical illness. ARDS may be seen in the setting of severe pulmonary (pneumonia) or systemic infection (sepsis), following trauma, multiple blood transfusions (TRALI), severe burns, severe inflammation of the pancreas (pancreatitis), near-drowning or other aspiration events, drug reactions, or inhalation injuries.[9] Some cases of ARDS are linked to large volumes of fluid used during post-trauma resuscitation.[10]

Diagnostic criteria for ARDS have changed over time as understanding of the pathophysiology has evolved. The international consensus criteria for ARDS were most recently updated in 2012 and are known as the "Berlin definition".[11][12] In addition to generally broadening the diagnostic thresholds, other notable changes from the prior 1994 consensus criteria[3] include discouraging the term "acute lung injury," and defining grades of ARDS severity according to degree of decrease in the oxygen content of the blood.

According to the 2012 Berlin definition, ARDS is characterized by the following:

lung injury of acute onset, within 1 week of an apparent clinical insult and with progression of respiratory symptoms

Note that the Berlin definition requires a minimum positive end expiratory pressure (PEEP) of 5 cmH2O for consideration of the PaO2/FiO2 ratio. This degree of PEEP may be delivered noninvasively with CPAP to diagnose mild ARDS.

Note that the 2012 "Berlin criteria" are a modification of the prior 1994 consensus conference definitions (see history).[13]

Radiologic imaging has long been a criterion for diagnosis of ARDS. Original definitions of ARDS specified that correlative chest X-ray findings were required for diagnosis, the diagnostic criteria have been expanded over time to accept CT and ultrasound findings as equally contributory. Generally, radiographic findings of fluid accumulation (pulmonary edema) affecting both lungs and unrelated to increased cardiopulmonary vascular pressure (such as in heart failure) may be suggestive of ARDS.
Ultrasound findings suggestive of ARDS include the following:

Neutrophils and some T-lymphocytes quickly migrate into the inflamed lung tissue and contribute in the amplification of the phenomenon. Typical histological presentation involves diffuse alveolar damage and hyaline membrane formation in alveolar walls. Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress.

Acute respiratory distress syndrome is usually treated with mechanical ventilation in the intensive care unit (ICU). Mechanical ventilation is usually delivered through a rigid tube which enters the oral cavity and is secured in the airway (endotracheal intubation), or by tracheostomy when prolonged ventilation (≥2 weeks) is necessary. The role of non-invasive ventilation is limited to the very early period of the disease or to prevent worsening respiratory distress in individuals with atypical pneumonias, lung bruising, or major surgery patients, who are at risk of developing ARDS. Treatment of the underlying cause is crucial. Appropriate antibiotic therapy is started as soon as culture results are available, or if infection is suspected (whichever is earlier). Empirical therapy may be appropriate if local microbiological surveillance is efficient. Where possible the origin of the infection is removed. When sepsis is diagnosed, appropriate local protocols are followed.

Previously, mechanical ventilation aimed to achieve tidal volumes (Vt) of 12–15 ml/kg (where the weight is ideal body weight rather than actual weight). Recent studies have shown that high tidal volumes can overstretch alveoli resulting in volutrauma (secondary lung injury). The ARDS Clinical Network, or ARDSNet, completed a clinical trial that showed improved mortality when people with ARDS were ventilated with a tidal volume of 6 ml/kg compared to the traditional 12 ml/kg. Low tidal volumes (Vt) may cause a permitted rise in blood carbon dioxide levels and collapse of alveoli[13] because of their inherent tendency to increase shunting within the lung. Physiologic dead space cannot change as it is ventilation without perfusion. A shunt is perfusion without ventilation.

Low tidal volume ventilation was the primary independent variable associated with reduced mortality in the NIH-sponsored ARDSnet trial of tidal volume in ARDS. Plateau pressure less than 30 cm H2O was a secondary goal, and subsequent analyses of the data from the ARDSnet trial and other experimental data demonstrate that there appears to be no safe upper limit to plateau pressure; regardless of plateau pressure, individuals with ARDS fare better with low tidal volumes.[17]

Positive end-expiratory pressure (PEEP) is used in mechanically ventilated people with ARDS to improve oxygenation. In ARDS, three populations of alveoli can be distinguished. There are normal alveoli which are always inflated and engaging in gas exchange, flooded alveoli which can never, under any ventilatory regime, be used for gas exchange, and atelectatic or partially flooded alveoli that can be "recruited" to participate in gas exchange under certain ventilatory regimens. The recruitable alveoli represent a continuous population, some of which can be recruited with minimal PEEP, and others which can only be recruited with high levels of PEEP. An additional complication is that some alveoli can only be opened with higher airway pressures than are needed to keep them open, hence the justification for maneuvers where PEEP is increased to very high levels for seconds to minutes before dropping the PEEP to a lower level. PEEP can be harmful; high PEEP necessarily increases mean airway pressure and alveolar pressure, which can damage normal alveoli by overdistension resulting in DAD. A compromise between the beneficial and adverse effects of PEEP is inevitable.

The 'best PEEP' used to be defined as 'some' cmH2O above the lower inflection point (LIP) in the sigmoidal pressure-volume relationship curve of the lung. Recent research has shown that the LIP-point pressure is no better than any pressure above it, as recruitment of collapsed alveoli—and, more importantly, the overdistension of aerated units—occur throughout the whole inflation. Despite the awkwardness of most procedures used to trace the pressure-volume curve, it is still used by some[who?] to define the minimum PEEP to be applied to their patients. Some new ventilators can automatically plot a pressure-volume curve.

PEEP may also be set empirically. Some authors[who?] suggest performing a 'recruiting maneuver'—a short time at a very high continuous positive airway pressure, such as 50 cmH2O (4.9 kPa)—to recruit or open collapsed units with a high distending pressure before restoring previous ventilation. The final PEEP level should be the one just before the drop in PaO2 or peripheral blood oxygen saturation during a step-down trial.

Intrinsic PEEP (iPEEP) or auto-PEEP—first described by John Marini of St. Paul Regions Hospital—is a potentially unrecognized contributor to PEEP in intubated individuals. When ventilating at high frequencies, its contribution can be substantial, particularly in people with obstructive lung disease such as asthma or chronic obstructive pulmonary disease (COPD). iPEEP has been measured in very few formal studies on ventilation in ARDS, and its contribution is largely unknown. Its measurement is recommended in the treatment of people who have ARDS, especially when using high-frequency (oscillatory/jet) ventilation.

The position of lung infiltrates in acute respiratory distress syndrome is non-uniform. Repositioning into the prone position (face down) might improve oxygenation by relieving atelectasis and improving perfusion. If this is done early in the treatment of severe ARDS, it confers a mortality benefit of 26% compared to supine ventilation.[20]

An NIH-sponsored multicenter ARDSnet study of corticosteroids that ran from August 1997 to November 2003 titled LaSRS for ARDS demonstrated that despite an improvement in cardiovascular physiology, methylprednisone is not efficacious in treatment for ARDS.[21][22]

Inhaled nitric oxide (NO) selectively widens the lung's arteries which allows for more blood flow to open alveoli for gas exchange. Despite evidence of increased oxygenation status, there is no evidence that inhaled nitric oxide decreases morbidity and mortality in people with ARDS.[23] Furthermore, nitric oxide may cause kidney damage and is not recommended as therapy for ARDS regardless of severity.[24]

Extracorporeal membrane oxygenation (ECMO) is mechanically applied prolonged cardiopulmonary support. There are two types of ECMO: Venovenous which provides respiratory support and venoarterial which provides respiratory and hemodynamic support. People with ARDS who do not require cardiac support typically undergo venovenous ECMO. Multiple studies have shown the effectiveness of ECMO in acute respiratory failure.[25][26][27] Specifically, the CESAR (Conventional ventilatory support versus Extracorporeal membrane oxygenation for Severe Acute Respiratory failure) trial[28] demonstrated that a group referred to an ECMO center demonstrated significantly increased survival compared to conventional management (63% to 47%).[29]

The annual incidence of ARDS is 13–23 people per 100,000 in the general population.[30] Its incidence in the mechanically ventilated population in intensive care units is much higher. According to Brun-Buisson et al (2004), there is a prevalence of acute lung injury (ALI) of 16.1% percent in ventilated patients admitted for more than 4 hours.

Worldwide, severe sepsis is the most common trigger causing ARDS.[31] Other triggers include mechanical ventilation, sepsis, pneumonia, Gilchrist's disease, drowning, circulatory shock, aspiration, trauma—especially pulmonary contusion—major surgery, massive blood transfusions,[32]smoke inhalation, drug reaction or overdose, fat emboli and reperfusion pulmonary edema after lung transplantation or pulmonary embolectomy. However, the majority of these patients with all these conditions mentioned do not develop ARDS.It is not clear why some people with the mentioned factors above don't get ARDS and some do.

Pneumonia and sepsis are the most common triggers, and pneumonia is present in up to 60% of patients and may be either causes or complications of ARDS. Alcohol excess appears to increase the risk of ARDS.[33] Diabetes was originally thought to decrease the risk of ARDS, but this has shown to be due to an increase in the risk of pulmonary edema.[34][35] Elevated abdominal pressure of any cause is also probably a risk factor for the development of ARDS, particularly during mechanical ventilation.[citation needed]

The death rate varies from 25–40% in centers using up-to-date ventilatory strategies and up to 58% in all centers.[36][37][38][39]

Acute respiratory distress syndrome was first described in 1967 by Ashbaugh et al.[13][40] Initially there was no clearly established definition, which resulted in controversy regarding the incidence and death of ARDS.

In 1988, an expanded definition was proposed, which quantified physiologic respiratory impairment.

In 2012, the Berlin Definition of ARDS was devised by the European Society of Intensive Care Medicine, and was endorsed by the American Thoracic Society and the Society of Critical Care Medicine. These recommendations were an effort to both update classification criteria in order to improve clinical usefulness, and to clarify terminology. Notably, the Berlin guidelines discourage the use of the term "acute lung injury" or ALI, as the term was commonly being misused to characterize a less severe degree of lung injury. Instead, the committee proposes a classification of ARDS severity as mild, moderate or severe according to arterial oxygen saturation.[11] The Berlin definitions represent the current international consensus guidelines for both clinical and research classification of ARDS.

There is ongoing research on the treatment of ARDS by interferon (IFN) beta-1a to aid in preventing leakage of vascular beds. Traumakine (FP-1201-lyo), is a recombinant human IFN beta-1a drug developed by Faron pharmaceuticals, is undergoing international phase-III clinical trials after an open-label, early-phase trial showed an 81% reduction-in-odds of 28-day mortality in ICU patients with ARDS.[43] The drug is known to function by enhancing lung CD73 expression and increasing production of anti-inflammatory adenosine, such that vascular leaking and escalation of inflammation are reduced.[44]

Aspirin has been studied in those who are at high risk and was not found to be useful.[1]